Research & Scholarship

Current Research and Scholarly Interests

I am interested in the prevention and control of critical care-related illnesses and complications, including ventilator-associated pneumonia, spread of nosocomial infections, and prognosis of multiple organ system failure in intensive care units. Infections and complications of therapy in immunocompromised hosts, including effects of chemotherapy and hematopoetic stem cell transplants is another interest.

Abstract

Patient safety remains a national priority, but the role of disease-specific characteristics in safety is not well characterized.We identified potentially preventable medical injuries using patient safety indicators (PSIs) and annual data from the Nationwide Inpatient Sample between 2003 and 2007. We compared the rate of selected PSIs among patients hospitalized with and without sepsis. Among patients with sepsis, we also compared PSI rates across severity strata. Using multivariable case-control matching and regression analyses, we estimated the excess adverse outcomes associated with PSI events in patients with sepsis.Patients hospitalized with sepsis accounted for 2% to 4% of hospital discharges; however, they accounted for 9% to 26% of all potential medical injuries. PSI rates varied considerably; among patients hospitalized for sepsis, they were lowest for accidental puncture or laceration and highest for postoperative respiratory failure. Nearly all PSI rates were higher among patients with sepsis compared with patients without sepsis. Among those with sepsis, most PSI rates increased as sepsis severity increased. Compared with matched sepsis control subjects, increased length of stay and hospital charges were associated with PSI events in sepsis cases. However, only decubitus ulcer, iatrogenic pneumothorax, and postoperative metabolic and physiologic derangement or respiratory failure were associated with excess mortality.Patients hospitalized for sepsis, compared with the general hospital population, were at a substantially increased risk of potential medical injury; their risk rose as disease severity increased. Future patient safety efforts may benefit from focusing on medically vulnerable populations.

Abstract

Patients with intensive care unit (ICU) transfers from hospital wards have higher mortality than those directly admitted from the emergency department.To describe the association between the timing of unplanned ICU transfers and hospital outcomes.Evaluation of 6369 early (within 24 hours of hospital admission) unplanned ICU transfer cases and matched directly admitted ICU controls from an integrated healthcare system. Cohorts were matched by predicted mortality, age, gender, diagnosis, and admission characteristics. Hospital mortality of cases and controls were compared based on elapsed time and diagnosis.More than 5% of patients admitted through the emergency department experienced an unplanned ICU transfer; the incidence and rates of transfers were highest within the first 24 hours of hospitalization. Multivariable matching produced 5839 (92%) case-control pairs. Median length of stay was higher among cases (5.0 days) than controls (4.1 days, P < 0.01); mortality was also higher among cases (11.6%) than controls (8.5%, P < 0.01). Patients with early unplanned transfers were at an increased risk of death (odds ratio, 1.44; 95% confidence interval, 1.26-1.64; P < 0.01); an increased risk of death was observed even among patients transferred within 8 hours of hospitalization. Hospital mortality differed based on admitting diagnosis categories. While it was higher among cases admitted for respiratory infections and gastrointestinal bleeding, it was not different for those with acute myocardial infarction, sepsis, and stroke.Early unplanned ICU transfers-even within 8 hours of hospitalization-are associated with increased mortality; outcomes vary by elapsed time to transfer and admitting diagnosis.

Abstract

The implementation of health information technology (HIT) is accelerating, driven in part by a growing interest in computerized physician order entry (CPOE) as a tool for improving the quality and safety of patient care. Computerized physician order entry could have a substantial impact on patients in intensive care, where the potential for medical error is high, and the clinical workflow is complex. In 2009, only 17% of hospitals had functional CPOE systems in place. In intensive care unit (ICU) settings, CPOE has been shown to reduce the occurrence of some medication errors, but evidence of a beneficial effect on clinical outcomes remains limited. In some cases, new error types have arisen with the use of CPOE. Intensive care unit workflow and staff relationships have been affected by CPOE, often in unanticipated ways. The design of CPOE software has a strong impact on user acceptance. Intensive care unit-specific order sets lessen the cognitive workload associated with the use of CPOE and improve user acceptance. The diffusion of new technological innovations in the ICU can have unintended consequences, including changes in workflow, staff roles, and patient outcomes. When implementing CPOE in critical care areas, both organizational and technical factors should be considered. Further research is needed to inform the design and management of CPOE systems in the ICU and to better assess their impact on clinical end points, cost-effectiveness, and user satisfaction.

Abstract

We performed a retrospective review to investigate pulmonary toxicity syndrome (PTS) in a cohort of breast cancer patients undergoing BCNU-containing high-dose chemotherapy (HDC). Our aim was to characterize presentation, identify risk factors, determine outcome following therapy, and find any association with differences in survival. We reviewed the data of 152 patients with stage II or III or metastatic breast cancer treated with cyclophosphamide 5625 mg/m2, cisplatin 165 mg/m2, and BCNU 600 mg/m2 followed by autologous peripheral blood hematopoietic cell transplantation. During follow-up, PTS was diagnosed when the following criteria were met: (1) presentation with typical clinical symptoms of PTS, (2) an absolute carbon monoxide diffusion capacity (DLCO) decline of 10% compared with pre-HDC DLCO, and (3) no clinical evidence of active pulmonary infection. Patients were then treated with a course of corticosteroid therapy. The incidence of PTS for all 152 patients was 59%, with a median onset at 45 days (range, 21-149 days) post-HDC. The median absolute DLCO decrement was 26% (range, 10%-73%) at diagnosis of PTS. There was no significant correlation between patient age, stage of breast cancer, pre-HDC chemotherapy regimen, pre-HDC chest wall radiotherapy, tobacco use, prior lung disease, or baseline pulmonary function test results and the development of PTS. We did observe an interesting association between PTS and the development of a noncholestatic elevation of transaminases. Of PTS patients treated with prednisone therapy for a median of 105.5 days (range, 44-300 days), 91% achieved resolution of their PTS without pulmonary sequelae. At 3 years, the overall survival (OS) of stage II or III patients who developed PTS was 84% (95% confidence interval [CI], 73%-95%); of metastatic breast cancer patients with PTS, the OS was 58% (95% CI, 38%-78%). These values were not significantly different from those of patients who did not develop PTS (91% [95% confidence interval [CI], 81%-100%] and 53% [95% CI, 32%-74%], respectively). No significant differences in disease-free or event-free survival were observed between patients with and without PTS. The incidence of PTS in breast cancer patients treated with a BCNU-containing HDC regimen can be remarkably high. Treatment with a course of corticosteroid therapy is successful in the vast majority.

Abstract

Airway complications of relapsing polychondritis (RP), including tracheobronchial stenosis, can be fatal. This paper describes a life-saving technique (placement of multiple metallic endobronchial stents under conscious sedation) to prevent life-threatening airway closure in a 50-year-old woman with RP. Using fluoroscopic and bronchoscopic guidance, a tracheal stent and three endobronchial metallic stents were deployed in the central airways, with good functional outcome. There were no complications. In critical airway compromise caused by RP, the insertion of endobronchial stents can result in improved symptoms, pulmonary function, and a return to daily activities, without the use of tracheotomy and mechanical ventilation.

Abstract

Immediate postoperative evaluation of the patient remains a crucial role of the intensivist. Postoperative patients can be divided into the otherwise healthy, chronically ill, and acutely ill for strategizing about care. For chronically ill and acutely ill patients who require ongoing ventilation, ventilator management continues to evolve toward modes that are more interactive with patient needs. Newer modes of ventilation are also being explored to protect the lung against damage attributable to mechanical ventilation. Weaning indexes and associated protocols have become more sophisticated and now allow physicians greater certainty in evaluating patients' readiness for extubation. This article will discuss factors to be considered prior to extubation as well as the latest ventilatory and weaning strategies.

Abstract

A patient with severe and protracted symptoms from intracranial hypotension is described. The patient's presentation was marked by diffuse encephalopathy and profound depression of consciousness. This case report expands the presently known clinical spectrum of this uncommon and generally benign illness. The clinical and laboratory findings typically observed in the syndrome of intracranial hypotension are outlined. The pathophysiological mechanisms of the phenomenon are briefly discussed. Intracranial hypotension is a potentially severe illness with specific treatments that are distinct from the treatment of most neurological diseases. Three cardinal features--postural headache, pachymeningitis, and descent of midline cerebral structures--should prompt the diagnosis.

Abstract

To determine the prevalence of unsuspected pulmonary embolism (PE) on routine thoracic helical computed tomographic (CT) scans and to quantify the improvement in PE detection by using a cine-paging mode on a workstation instead of hard-copy review.Seven hundred eighty-five patients referred for routine contrast medium-enhanced thoracic CT within 9 months were prospectively recruited. Helical CT was performed. Studies were prospectively interpreted by four radiologists. Two radiologists performed routine, undirected, hard-copy consensus review for official interpretation; two of three thoracic radiologists independently performed a dedicated workstation-based search for PE. The presence of PE involving the main, lobar, or segmental pulmonary arteries was assigned a score of 1-5 (1 = definitely negative, 5 = definitely positive) by each independent reviewer. Patients with a score of 4 or 5 underwent lower-extremity ultrasound, ventilation-perfusion scintigraphy, or both, followed by pulmonary CT angiography if the findings were still equivocal.Twelve (1.5%) of the 785 patients had unsuspected PE, with an inpatient prevalence of 5% (eight of 160) and an outpatient prevalence of 0.6% (four of 625). Of the 12 patients with unsuspected PE, 10 (83%) had cancer. Of the 81 inpatients with cancer, seven (9%) had unsuspected PE. A dedicated workstation-based search resulted in detection of PE in three more patients (25%) than did hard-copy interpretation.The prevalence of unsuspected PE was highest among inpatients with cancer. A directed, workstation-based search can improve the PE detection rate over that with hard-copy review.

Abstract

The specific diagnosis of interstitial lung disease has conventionally been determined by lung biopsy. Lung biopsy also is useful for assessing disease activity and prognosis, and is sometimes useful in deciding on the necessity of therapy. The availability of newer biopsy techniques and the interaction of these techniques with current generation imaging modalities has changed the role of biopsy in interstitial lung disease. This review reports on the indications, techniques, and limitations of biopsy procedures and places them in the context of the use of current imaging methods, as reflected in recent literature.

Abstract

Because each of very different treatments for Hodgkin's disease (HD) may result in a high rate of cure, attention is currently focused on toxicity. This prospective study was designed to assess the effects of mediastinal irradiation and bleomycin chemotherapy on pulmonary function.Patients were treated from 1980 to 1990 on randomized controlled trials at Stanford University. Pulmonary function was tested before treatment (baseline), early after treatment (< 15 months), and more than 36 months posttherapy. Treatment options in the 145 patients were grouped as I (mediastinal radiotherapy), II (mediastinal radiotherapy plus bleomycin), and III (bleomycin) for analyses of variance (ANOVAs). A variety of regression models were used to predict early and late effects on pulmonary function.A decrease in forced vital capacity (FVC) and diffusing capacity (DLCO) in the first 15 months after treatment followed by recovery after 36 months was observed for most patients. Patients who received mediastinal radiotherapy (RT) had a more pronounced reduction in pulmonary function and less complete recovery. Overall, 3 or more years after treatment, 32% of group I patients, 37% of group II patients, and 19% of group III patients had FVC values less than 80% of predicted, while only 7% of patients had a DLCO less than 80% of predicted. Linear regression identified baseline measurement as the only significant predictor of change in percent predicted FVC or DLCO; patients with higher baseline values had greater decrements after therapy. Mantle RT was the only significant treatment variable, predictive of FVC and DLCO within 15 months and FVC at 36 or more months. No patient experienced pulmonary toxicity severe enough to require hospitalization.This prospective analysis of pulmonary function after treatment for HD showed that mediastinal RT was the only treatment variable that achieved statistical significance. Although there were no significant interactions between mediastinal RT and bleomycin or Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy, the patient numbers were small after correction for mediastinal mass size and drug regimen such that an effect could have been missed. The mild reduction in pulmonary function should be factored into the overall assessment of morbidity risk for each of the potentially curative treatments included in this study. As with all reports of late effects, these data should be interpreted with respect to the population tested, details of the treatment administered, methods of measurement, and length of follow-up.

Abstract

It is widely believed that thoracotomy is necessary to obtain biopsy specimens adequate for the histopathologic demonstration of pulmonary Wegener's granulomatosis (WG). We report five patients with WG who were diagnosed by transbronchial biopsy (TBB). In three cases, a diagnosis of WG was made by TBB alone. In the other two patients, subsequent open lung biopsies confirmed the TBB findings but did not add essential diagnostic information. Our experience suggests TBB may be appropriate as the initial diagnostic procedure in selected cases of suspected WG. This approach requires an understanding of the diverse histologic features of WG and the correlation of clinical and pathologic data.

Abstract

Although Toxoplasma gondii multiplies within normal murine alveolar and peritoneal macrophages, it is killed by normal rat alveolar and peritoneal macrophages. The killing by rat macrophages is by a nonoxidative mechanism. Studies on normal human alveolar macrophages have reported disparate results in regard to their ability to inhibit or kill T. gondii. We considered it of interest to explore further the effect of normal human alveolar and peritoneal macrophages on T. gondii. Unstimulated alveolar macrophages from each of seven individuals demonstrated a marked ability to kill or inhibit multiplication of T. gondii in vitro (e.g., the number of parasites per 100 alveolar macrophages was 31 at time zero and 2 at 18 h, whereas this value increased from 37 at time zero to 183 at 18 h in murine macrophages assayed in parallel). In quantitative assays of superoxide, alveolar macrophages released a substantial amount of superoxide when exposed to phorbol myristate acetate or to candidae. In contrast, alveolar macrophages incubated with T. gondii released no more superoxide than when in medium alone. Scavengers of superoxide anions, hydrogen peroxide, singlet oxygen, and hydroxyl radicals failed to inhibit killing of T. gondii by alveolar macrophages. Peritoneal macrophages from each of six normal women undergoing laparoscopy killed T. gondii in vitro; results of quantitative superoxide assays and scavenger experiments demonstrated that no oxidative burst was triggered in these macrophages by exposure to T. gondii. These data indicate that normal human alveolar and peritoneal macrophages can kill an intracellular parasite by nonoxidative mechanisms and suggest that these mechanisms are important in inhibition or killing of other opportunistic intracellular pathogens.

Abstract

Cancer of the lung is rapidly increasing in incidence in both sexes and soon will overtake breast cancer as the most deadly cancer in women. Selection of patients with non-small-cell carcinoma for surgical resection is largely based on preoperative clinical staging, using the American Joint Committee on Cancer's TNM-based group staging protocol. Determining the presence or absence of mediastinal nodal metastasis is paramount and is currently best achieved by computed tomographic scanning of the chest and biopsy of enlarged nodes via mediastinoscopy. Certain types of stage III lesions, previously excluded from surgical treatment, are now recognized as operable.